I am an emergency physician on staff at Lenox Hill Hospital in New York City, where I have practiced for the past 10 years. I also serve as an adviser to Medscape Emergency Medicine, an educational portal for physicians, and an affiliate of WebMD. My other time is spent with my private house call practice called DR 911, providing medical care to both travelers and residents in Manhattan. I have a keen interest in medical technology and public health education.

Genetic Biomarker Identified That May Predict Suicide Risk

Investigators from Johns Hopkins University School of Medicine have identified a unique modification to a gene linked to stress reactions that may potentially lead in the near future to a blood test to evaluate a person’s risk of attempting suicide.

Their findings were published July 30 in The American Journal of Psychiatry.

The researchers found changes in a gene regulating the brain’s response to stress hormones that may help doctors determine who may be at risk for suicidal thoughts and behaviors.

“Suicide is a major preventable public health problem, but we have been stymied in our prevention efforts because we have no consistent way to predict those who are at increased risk of killing themselves,” said lead author, Zachary Kaminsky, Ph.D., an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. “With a test like ours, we may be able to stem suicide rates by identifying those people and intervening early enough to head off a catastrophe.”

Researchers evaluated a specific genetic mutation in a gene known as SKA2. Comparing brain samples from healthy people and those with psychiatric ailments, investigators found that levels of SKA2 were greatly diminished in those who committed suicide.

In the SKA mutation, researchers identified an epigenetic modification, or addition of specific molecule, that changed SKA2 gene function, but left the gene’s underlying DNA sequence unchanged. The specific aforementioned change added methyl groups to the gene. It turns out that higher levels of methylation were subsequently noted in the same study participants whom had committed suicide. The higher levels of methylation, seen in persons whom committed suicide, were then observed in two independent groups of patients who were evaluated in the study.

Another part of the study involving 325 participants found similar methylation increases at SKA2 in individuals with suicidal thoughts or attempts. Their model analysis accurately predicted–with 80 percent certainty—those with suicidal thoughts or attempted suicide. Participants with a higher risk for suicide had a 90 percent accuracy based on results. And based on the results of blood tests, researchers were able to predict with 96 percent accuracy those persons who had attempted suicide.

The SKA2 gene, expressed in the prefrontal cortex of the brain, is involved in inhibiting negative thoughts and controlling impulsive behavior. SKA2 is specifically responsible for allowing stress hormone receptors into a cell’s nuclei to perform its function. If there isn’t enough SKA2, or it is altered in some way, the stress hormone receptor is unable to suppress the release of cortisol throughout the brain. Previous research has shown that such cortisol release is abnormal in those who attempt or complete suicide.

Kaminsky reasoned that a test based on the findings in this research could potentially be utilized to predict future suicide attempts in those who suffer from mental illness. It might also be used to limit availability of firearms among those at risk, and to make decisions about the urgency for evaluation and intervention in those at risk for suicidal behaviors.

Kaminsky also explained that it would likely be valuable for the military to check soldiers for the gene mutation that could place them at higher risk. Those who are at risk could then be more closely monitored when they returned home after deployment. A blood test used to detect the at-risk gene might also be valuable in the emergency department to assess risk for suicide in patients presenting with concerning symptoms and unknown to medical providers.

“We have found a gene that we think could be really important for consistently identifying a range of behaviors from suicidal thoughts to attempts to completions,” Kaminsky said. “We need to study this in a larger sample but we believe that we might be able to monitor the blood to identify those at risk of suicide.”

One expert agreed that the findings of this study may offer the potential for clear advances in the future.

“Dr. Guintivano and his colleagues have elegantly demonstrated how much the field of psychiatric and behavioral genetics has evolved over the last ten years, said Dr. Aaron Krasner, Adolescent Transitional Living Program Service Chief at Silver Hill Hospital in New Canaan, CT.

“With increasingly sophisticated technology, more nuanced appreciation of the science of genetic signaling, and more refined clinical phenotypes, the finding that increased methylation at SKA2 among suicide decedents merits attention, replication, and represents a significant contribution to the enormously challenging scientific project of correlating biological underpinnings to complex human behaviors,” explained Krasner.

“Aside from the elegant science, Dr. Guintivano interrelates and elucidates three crucial, and clinically relevant principles in his paper: the biological basis of epigenetics (i.e., the nature/nurture debate), the need to utilize clinical samples in the suicide field (which is a huge challenge), and the lucid but chronically elusive link between the mind and the body,” (i.e., psychoendocrinology), added Krasner.

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